ORIGINAL ARTICLE: HEPATOLOGY
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NUTRITION
rhBSSL Improves Growth and LCPUFA Absorption in Preterm Infants Fed Formula or Pasteurized Breast Milk Charlotte Casper, yVirgilio P. Carnielli, zJean-Michel Hascoet, §Alexandre Lapillonne, Luca Maggio, ôKristina Timdahl, ôBirgitta Olsson, ôMa˚rten Va˚gero¨, and #Olle Hernell
jj
ABSTRACT Objectives: Preterm infants often experience suboptimal growth, which can affect organ development. The aim of this study was to improve growth by treatment with bile salt–stimulated lipase (BSSL), naturally present in breast milk, but lost after pasteurization, and absent in formula. Methods: Two clinical trials were performed with a predefined analysis of combined data to investigate the effects of recombinant human BSSL (rhBSSL) treatment on growth velocity and fat absorption in preterm infants. The studies were randomized and double-blinded comparing 7-day treatment with rhBSSL and placebo, administered in pasteurized breast milk or formula, using a crossover design. Results: Sixty-three infants were evaluated for safety. At randomization, the mean (standard deviation) weight was 1467 (193) g and mean postmenstrual age was 32.6 (0.5) weeks. Sixty and 46 infants were evaluated for growth velocity and fat absorption, respectively. rhBSSL treatment significantly improved mean growth velocity by 2.93 g kg1 day1 (P < 0.001) Received October 16, 2013; accepted February 28, 2014. From the Unit of Neonatology, Children’s Hospital, Paul Sabatier University Toulouse, Toulouse, France, the yDivision of Neonatology, Polytechnic University of Marche and Salesi’s Children Hospital, Ancona, Italy, the zDepartment of Neonatology, Maternite Regionale, Universite´ de Lorraine, Nancy, the §Department of Neonatology, Assistance Publique Hoˆpitaux de Paris Necker Hospital, Paris Descartes University, Paris, France, the jjDivision of Neonatology, Department of Pediatrics, Catholic University Sacred Heart, Rome, Italy, the ôSwedish Orphan Biovitrum (Sobi), Stockholm, and the #Department of Clinical Sciences, Pediatrics, Umea˚ University, Umea˚, Sweden. Address correspondence and reprint requests to Kristina Timdahl, Medical Director, Swedish Orphan Biovitrum (Sobi), SE-112 76 Stockholm, Sweden (e-mail: [email protected]). Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.jpgn.org). www.clinicaltrials.gov registration no: NCT00658905 and NCT00659243. The preterm formula study was carried out partially with research funding from the European Community’s Sixth Framework Program (the Early Nutrition Programming [EARNEST]) using a formula provided by Ordesa. Swedish Orphan Biovitrum (Sobi) provided the remainder of the funding for the 2 phase II studies and their analysis. O.H., A.L., C.C., V.P.C. are consultants to Sobi for the rhBSSL project. K.T., B.O., and M.V. are employed by Sobi and holders of company shares. The other authors report no conflicts of interest. Copyright # 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. This is an open-access article distributed under the terms of the Creative Commons AttributionNonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work, provided it is properly cited. The work cannot be changed in any way or used commercially. DOI: 10.1097/MPG.0000000000000365
JPGN
Volume 59, Number 1, July 2014
compared with placebo (mean 16.86 vs 13.93 g kg1 day1) and significantly decreased the risk of suboptimal growth (24,000 preterm infants has highlighted that the proportion of infants whose weight is
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NUTRITION
rhBSSL Improves Growth and LCPUFA Absorption in Preterm Infants Fed Formula or Pasteurized Breast Milk Charlotte Casper, yVirgilio P. Carnielli, zJean-Michel Hascoet, §Alexandre Lapillonne, Luca Maggio, ôKristina Timdahl, ôBirgitta Olsson, ôMa˚rten Va˚gero¨, and #Olle Hernell
jj
ABSTRACT Objectives: Preterm infants often experience suboptimal growth, which can affect organ development. The aim of this study was to improve growth by treatment with bile salt–stimulated lipase (BSSL), naturally present in breast milk, but lost after pasteurization, and absent in formula. Methods: Two clinical trials were performed with a predefined analysis of combined data to investigate the effects of recombinant human BSSL (rhBSSL) treatment on growth velocity and fat absorption in preterm infants. The studies were randomized and double-blinded comparing 7-day treatment with rhBSSL and placebo, administered in pasteurized breast milk or formula, using a crossover design. Results: Sixty-three infants were evaluated for safety. At randomization, the mean (standard deviation) weight was 1467 (193) g and mean postmenstrual age was 32.6 (0.5) weeks. Sixty and 46 infants were evaluated for growth velocity and fat absorption, respectively. rhBSSL treatment significantly improved mean growth velocity by 2.93 g kg1 day1 (P < 0.001) Received October 16, 2013; accepted February 28, 2014. From the Unit of Neonatology, Children’s Hospital, Paul Sabatier University Toulouse, Toulouse, France, the yDivision of Neonatology, Polytechnic University of Marche and Salesi’s Children Hospital, Ancona, Italy, the zDepartment of Neonatology, Maternite Regionale, Universite´ de Lorraine, Nancy, the §Department of Neonatology, Assistance Publique Hoˆpitaux de Paris Necker Hospital, Paris Descartes University, Paris, France, the jjDivision of Neonatology, Department of Pediatrics, Catholic University Sacred Heart, Rome, Italy, the ôSwedish Orphan Biovitrum (Sobi), Stockholm, and the #Department of Clinical Sciences, Pediatrics, Umea˚ University, Umea˚, Sweden. Address correspondence and reprint requests to Kristina Timdahl, Medical Director, Swedish Orphan Biovitrum (Sobi), SE-112 76 Stockholm, Sweden (e-mail: [email protected]). Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.jpgn.org). www.clinicaltrials.gov registration no: NCT00658905 and NCT00659243. The preterm formula study was carried out partially with research funding from the European Community’s Sixth Framework Program (the Early Nutrition Programming [EARNEST]) using a formula provided by Ordesa. Swedish Orphan Biovitrum (Sobi) provided the remainder of the funding for the 2 phase II studies and their analysis. O.H., A.L., C.C., V.P.C. are consultants to Sobi for the rhBSSL project. K.T., B.O., and M.V. are employed by Sobi and holders of company shares. The other authors report no conflicts of interest. Copyright # 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. This is an open-access article distributed under the terms of the Creative Commons AttributionNonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work, provided it is properly cited. The work cannot be changed in any way or used commercially. DOI: 10.1097/MPG.0000000000000365
JPGN
Volume 59, Number 1, July 2014
compared with placebo (mean 16.86 vs 13.93 g kg1 day1) and significantly decreased the risk of suboptimal growth (24,000 preterm infants has highlighted that the proportion of infants whose weight is
